Life Extension Magazine®
There is increasing interest about the potential benefits of ingesting small amounts of a mineral called lithium.
In animal models, lithium has been shown to extend lifespan1,2—by as much as 46% in one study.3
A 2024 review of observational studies concluded that trace lithium levels in drinking water may reduce the incidence and mortality rates associated with dementia.4
In one clinical study, a daily dose of 300 mcg of lithium decreased cognitive decline in patients with Alzheimer’s disease, compared to a placebo.5
Trace amounts or microdoses of lithium may play a role in promoting healthy aging.
Understanding Lithium’s Benefits
For centuries, people have made pilgrimages to lithium-rich mineral springs,6 believing that drinking and bathing in the water had a positive effect on mood and overall health.
In the mid-20th century, researchers discovered that high doses of lithium could effectively treat bipolar disorder and certain forms of depression.7
While higher doses of lithium are used as prescription treatments for bipolar and psychiatric illnesses6,8 multiple studies suggest that trace amounts of lithium in drinking water may be associated with body-wide health benefits.4,9-11
A recent review of preclinical and clinical studies suggests that low-dose lithium may support cardiovascular, musculoskeletal, metabolic, and cognitive functions in aging individuals.10 One research group reported striking findings: long-term intake of trace amounts of lithium from drinking water was associated with reduced risk of all-cause mortality.11,12
In addition, several aspects of mental and physical health have been found to be better in areas where the water supply naturally contains trace amounts of lithium.8,10
A review of recent preclinical and clinical literature suggests that lithium can have beneficial effects on mechanisms related to:10
- Metabolic diseases like diabetes,
- Death due to cardiovascular disease,
- Death due to Alzheimer’s disease, and
- Death due to any cause.
Scientists have estimated that at low doses of just 1,000 mcg (or 1 mg) daily, lithium plays crucial roles in human biology.13 Many scientists working in this field now believe that low-dose lithium supports multiple body systems and aspects of health,10,14 especially for those at risk of dementia.4
A recent systematic review of five observational studies examined the association between trace levels of lithium in drinking water and risk of dementia. The findings suggest that the presence of trace lithium levels in drinking water, at concentrations between 2 mcg to 56 mcg per liter, is associated with a lower risk of dementia incidence and mortality.4
How Lithium Works
Preclinical studies have revealed mechanisms through which lithium may provide wide-ranging health benefits.8,10
Its most important effect appears to be on an enzyme known as GSK-3 (glycogen synthase kinase-3).
Increased GSK-3 activity is linked to metabolic disorders (diabetes), neurological (Alzheimer’s) and mood disorders, as well as some cancers.1,15 Drugs and nutrients that inhibit activity of GSK-3 have the potential to help prevent these conditions.
Scientists investigating methods to reduce GSK-3 activity discovered that lithium is among the most effective GSK-3 inhibitors.15
Other ways that lithium may counter mechanisms of aging and disease include:
- Enhancing transport of nutrients into brain cells,13
- Activating autophagy (cellular house- keeping),8,16
- Preventing abnormal accumulations of the proteins tau and beta-amyloid, which are associated with neurodegeneration,8
- Increasing brain-derived neurotrophic factor,13,16 a signaling molecule that protects brain cells and supports their function,
- Helping to maintain longer telomeres3,16 (protective caps on the ends of chromosomes tied to increased longevity),
- Protecting against threats to brain function, including glutamate toxicity,1
- Augmenting immune cell function,8 and
- Inducing stem cell growth.13
Lithium administration has also been shown to extend lifespan in roundworms and fruit flies. In one study, lithium increased the lifespan of worms by an astonishing 46%.3
Many researchers are enthusiastic about the potential of safe microdose or trace amounts of lithium for supporting longevity and healthy aging.1,9,10,14 However, further studies and human trials are needed to clarify existing findings.
Human Trials of Lithium
To date, most lithium trials in humans have focused on potential brain-health benefits. In subjects with both mild cognitive impairment and Alzheimer’s disease, lithium has improved cognitive performance and stabilized disease progression.
A randomized controlled trial showed the potential of microdose lithium.
In this study, a daily dose of just 300 mcg of lithium was given to Alzheimer’s patients for 15 months. While a placebo group continued to show deterioration in mental function, those receiving lithium stabilized throughout the course of the study.5
What You Need To Know
Health Benefits of Low-Dose Lithium
- The mineral lithium has long been used at high doses to treat mental health conditions. Scientists now are encouraged that low doses may support healthy aging and longevity.
- In observational studies, those with regular intake of small amounts of lithium in their drinking water have lower rates of death from any cause.
- In animal studies, lithium has been shown to extend a healthy lifespan.
- In a clinical study, microdose lithium intake for 15 months stabilized cognitive function in patients with Alzheimer’s disease, preventing the expected decline in mental abilities.
In a placebo-controlled trial, 45 patients with mild cognitive impairment who were given lithium daily in high doses of 150 mg, 300 mg, 450 mg, or 600 mg for a year had significantly improved cognitive performance and attention on tasks, compared to those who took a placebo. Cerebrospinal fluid levels of hyperphosphorylated tau—an abnormal protein that serves as a hallmark of Alzheimer’s disease—were reduced in participants taking lithium.17
In a later randomized controlled trial by this same research group, older adults with mild cognitive impairment received one of the four doses of lithium mentioned above, or placebo for two years; after completing the study, participants were followed for an additional two years. The placebo group continued to suffer cognitive and functional declines, while those receiving lithium remained stable over the entire study.18
Another meta-analysis of eight clinical studies compared efficacy and tolerability of high-dose lithium treatment with the newer class of monoclonal antibody Alzheimer’s drugs. This study found that lithium treatment may be safer than available monoclonal antibody medications.19
Summary
Low-dose lithium has considerable promise for lowering rates of cardiovascular disease, cognitive disorders, metabolic disease, and death from any cause.
In a clinical trial, microdose lithium stabilized cognitive function in patients with Alzheimer’s disease, preventing the expected decline in mental abilities.
A growing number of scientists believe that a small amount of daily lithium can help promote healthy aging, cognitive wellness, and more.
If you have any questions on the scientific content of this article, please call a Life Extension Wellness Specialist at 1-866-864-3027.
References
- Castillo-Quan JI, Li L, Kinghorn KJ, et al. Lithium Promotes Longevity through GSK3/NRF2-Dependent Hormesis. Cell Rep. 2016 Apr 19;15(3):638-50.
- Zarse K, Terao T, Tian J, et al. Low-dose lithium uptake promotes longevity in humans and metazoans. Eur J Nutr. 2011 Aug;50(5):387-9.
- Coutts F, Palmos AB, Duarte RRR, et al. The polygenic nature of telomere length and the anti-ageing properties of lithium. Neuropsychopharmacology. 2019 Mar;44(4):757-65.
- Fraiha-Pegado J, de Paula VJR, Alotaibi T, et al. Trace lithium levels in drinking water and risk of dementia: a systematic review. Int J Bipolar Disord. 2024 Aug 30;12(1):32.
- Nunes MA, Viel TA, Buck HS. Microdose lithium treatment stabilized cognitive impairment in patients with Alzheimer’s disease. Curr Alzheimer Res. 2013 Jan;10(1):104-7.
- Shorter E. The history of lithium therapy. Bipolar Disord. 2009 Jun;11 Suppl 2(Suppl 2):4-9.
- Snitow ME, Bhansali RS, Klein PS. Lithium and Therapeutic Targeting of GSK-3. Cells. 2021 Jan 28;10(2).
- Rybakowski JK. Antiviral, immunomodulatory, and neuroprotective effect of lithium. J Integr Neurosci. 2022 Mar 23;21(2):68.
- Terao T. Is lithium potentially a trace element? World J Psychiatry. 2015 Mar 22;5(1):1-3.
- Hamstra SI, Roy BD, Tiidus P, et al. Beyond its Psychiatric Use: The Benefits of Low-dose Lithium Supplementation. Curr Neuropharmacol. 2023;21(4):891-910.
- Fajardo VA, LeBlanc PJ, Fajardo VA. Trace lithium in Texas tap water is negatively associated with all-cause mortality and premature death. Appl Physiol Nutr Metab. 2018 Apr;43(4):412-4.
- Toffol E, Hatonen T, Tanskanen A, et al. Lithium is associated with decrease in all-cause and suicide mortality in high-risk bipolar patients: A nationwide registry-based prospective cohort study. J Affect Disord. 2015 Sep 1;183:159-65.
- Marshall PD. Lithium as a Nutrient. Journal of American Physicians and Surgeons. 2015;20.
- Szklarska D, Rzymski P. Is Lithium a Micronutrient? From Biological Activity and Epidemiological Observation to Food Fortification. Biol Trace Elem Res. 2019 May;189(1):18-27.
- Wang L, Li J, Di LJ. Glycogen synthesis and beyond, a comprehensive review of GSK3 as a key regulator of metabolic pathways and a therapeutic target for treating metabolic diseases. Med Res Rev. 2022 Mar;42(2):946-82.
- Gogoleva IV, Gromova OA, Torshin IY, et al. The neurobiological role of lithium salts. Neurosci Behav Physiol. 2023;53:939-45.
- Forlenza OV, Diniz BS, Radanovic M, et al. Disease-modifying properties of long-term lithium treatment for amnestic mild cognitive impairment: randomised controlled trial. Br J Psychiatry. 2011 May;198(5):351-6.
- Forlenza OV, Radanovic M, Talib LL, et al. Clinical and biological effects of long-term lithium treatment in older adults with amnestic mild cognitive impairment: randomised clinical trial. Br J Psychiatry. 2019 Nov;215(5):668-74.
- Terao I, Kodama W. Comparative efficacy, tolerability and acceptability of donanemab, lecanemab, aducanumab and lithium on cognitive function in mild cognitive impairment and Alzheimer’s disease: A systematic review and network meta-analysis. Ageing Res Rev. 2024 Feb;94:102203.